The invention relates to controlling ion populations provided by pulsed ion sources for subsequent processing, manipulation, and/or analysis. In particular, this invention relates to controlling ion populations provided by a pulsed ion source in ion storage type mass analyzers, such as radio frequency (RF) quadrupole ion trap mass spectrometers.
Ion storage type mass analyzers, such as RF quadrupole ion traps, ICR (Ion Cyclotron Resonance) and FTICR (Fourier Transform Ion Cyclotron Resonance) mass analyzers, function by transferring generated ions via an ion optical means to the storage/trapping cells on the mass analyzer, where the ions are then analyzed. One of the major factors that limit the mass resolution, mass accuracy and the reproducibility in such devices is space charge, which can alter the storage, trapping conditions, or ability to mass analyze of an ICR or ion trap, from one experiment to the next, and consequently vary the results attained.
One way to improve the reproducibility of results, the mass resolution and accuracy in ion storage type devices is to control the ion population that is stored/trapped, or otherwise confined, and subsequently analyzed in the mass analyzer.
Space charge effects arise from the influence of the electric fields of ions confined in the analyzer device upon each other. At very high levels of space charge, the mass resolution obtainable will deteriorate, and spectral peaks will shift in m/z. The greatest scan to scan variation in the magnitude of the space charge effect arises from differences in trapped ion numbers or population, caused by variations in the brightness of the source of ions (flux of ions). Unless space charge is either taken into account or regulated, high mass resolution and mass accuracy measurements can not be reliably achieved.
Optimum performance can relate to different criteria, such as avoidance of an excessive space charge, space charge constancy over a number of measurements, adaptation to special characteristics of the mass analyzer, and the like. Hence the optimum performance of a device is generally defined by an upper and a lower limit of ion population. Thus, for example, for low ion populations in the mass analyzer, it can be difficult to differentiate the detected population of ions from the noise level. Increasing the population of ions in the analysis chamber of the mass analyzer can avoid this problem. For high ion populations in the mass analyzer, increasing the population of ions too far can lead to space charge problems, resulting in deterioration in m/z assignment accuracy.
Different ion sources can be used in conjunction with mass analyzers. These include pulsed ion sources, which, as used in this specification, are ion sources that are operable to provide non-continuous ionization events (resulting in ion pulses or packets) separated by periods when ionization events are minimized, such as sources that use lasers to desorb analyte molecules from a surface. Common examples of such sources are the matrix assisted laser desorption ionization (MALDI) ion source as illustrated in FIG. 1, or the surface enhanced desorption ionization (SELDI) ion source. In this ionization method, molecules of an analyte are embedded in a layer of crystals of a typically low-molecular weight matrix substance, and this “sample” is typically disposed on a sample plate.
A laser pulse 105 (typically a pulse of a few nanoseconds duration) is directed at the sample plate 110 and provides energy to desorb both the matrix 115 and analyte 120, and to obtain efficient generation of analyte ions, without decomposing the analyte molecules. The power of the laser pulse is selected to optimize the signal of the mass analyzer. The matrix 115 plays a key role in this technique by absorbing the laser light energy and causing part of the illuminated substrate to vaporize. The matrix molecules absorb most of the incident laser energy, minimizing sample damage and fragmentation. The host matrix is selected to absorb radiation at the wavelength of the laser being used. The vapor cloud 125 that is produced is initially under substantially high pressure, occupying relatively little space. However, the vapor cloud eventually begins to expand into the (typically) evacuated chamber in which it has been generated.
Because it uses a laser pulse to generate the ions, a MALDI source 100 therefore produces ions in a pulsed fashion, in ion packets. Each packet represents a pulse within which the ions are distributed spatially. An ion packet comprises ions derived from the ions generated from the MALDI ion source. As used in this specification, ions “derived from” ions provided by a source of ions include the ions generated by a source of ions as well as ions generated by manipulation of those ions as will be discussed in more detail below.
The surfaces of the analyte/matrix mixture on the sample plate can be quite inhomogeneous, which can lead to signal variations over the surface of the target.
Once the sample ions and molecules are vaporized and ionized, they transfer electrostatically into the mass analyzer, for example a two or three dimensional quadrupole ion trap or a Fourier Transform Mass Spectrometer(FT-MS), where they are separated from the matrix ions, are individually detected based on their mass-to-charge (m/z) ratios, and analyzed.
In general, the optimum performance of the ion trap mass analyzer is achieved when the ion population generated in a single or multiple laser shots is characterized by maximum signal/noise ratio, but still is below the threshold of onset of significant space charge effects.